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Biomedical subjects

D Torre

Publications and source records attributed to D Torre.

At least 37 records · Page 2Linked to original sources

A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.

AIMS OF THE STUDY: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). PATIENTS AND METHODS: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. RESULTS: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. CONCLUSIONS: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

AIDS-Related Opportunistic Infections↗

A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.

To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.

AIDS-Related Opportunistic Infections↗

Serum levels of Fas/Apo-1 and Bcl-2 in children with HIV-1 infection.

Apoptosis of CD4-positive T cells is considered to be involved in depletion of CD4-positive T cells in adult patients with HIV-1 infection. In this report we evaluated serum levels of soluble Fas/Apo-1 and circulating bcl-2 protein (an antiapoptotic molecule) in HIV-1-infected children, and 30 HIV-1 seronegative children. Significantly higher levels of Fas/Apo-1 were observed in 13 HIV-1-infected children than in non-infected control children (p < 0.001), whereas serum levels of bcl-2 were significantly decreased (p=0.002). Seronegative children born to HIV-infected mothers displayed significantly decreased (p < 0.05) serum levels of bcl-2. By contrast, children born to HIV-seronegative mothers and suffering from acute lower respiratory infection had normal levels of bcl-2 and Fas/Apo-1. These data suggest that upregulation of Fas/Apo-1 along with downregulation of bcl-2 protein may contribute to apoptosis in children with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group.

The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.

AIDS-Related Opportunistic Infections↗

Population pharmacokinetics of rifabutin in human immunodeficiency virus-infected patients.

Rifabutin pharmacokinetics were studied by the population approach (NONMEM) with 40 human immunodeficiency virus-infected patients receiving rifabutin at different doses for prophylaxis or therapy of mycobacterial infections. A two-compartment open model with first-order absorption was used as the structural pharmacokinetic model. Parameter estimates were the absorption rate constant (0. 201/h), clearance/bioavailability (CL/F; 60.9 liters/h), volume of the central compartment/bioavailability (231 liters), intercompartmental clearance (60.3 liters/h), and volume of the peripheral compartment/bioavailability (Vp/F; 1,050 liters). The distribution and elimination half-lives were 1.24 and 25.4 h, respectively. The covariates tested for influence on CL/F and Vp/F were sex, age, weight, height, body surface area, tobacco smoking, drug addiction, alanine aminotransferase levels, creatinine clearance, total protein, bilirubin, numbers of CD4(+) cells, presence of diarrhea, cachexia index, rifabutin use (prophylaxis versus therapy), rifabutin dose, study site, and the concomitant administration of clarithromycin, fluconazole, phenobarbital, ciprofloxacin, azithromycin, or benzodiazepines. The only statistically significant effects on rifabutin pharmacokinetic parameters were a 27% decrease in Vp/F due to the concomitant administration of azithromycin and a 39% increase in Vp/F due to tobacco smoking. Such effects may be considered clinically unimportant. Our results confirm the lack of a correlation of rifabutin pharmacokinetic parameters with parameters of disease progression and gastrointestinal function. Also, the lack of a correlation with covariates which were previously found to be significant, such as concomitant fluconazole and clarithromycin use, may suggest that the effect of such covariates may be less important in the real clinical setting, in which several concomitant factors may influence pharmacokinetic parameters, with an overall effect of no apparent correlation.

Adult↗

Expression of fibronectin and its receptor in some tumour cell lines and in HIV-1-infected cells.

The aim of our study was to evaluate the levels of fibronectin (FN) and its classic receptor (FNR) in various transformed cells lines, especially of leukemic origin, and also the influence of HIV-1 replication on the expression of these proteins (in particular on H9-V cells, chronically infected with HIV-1, and acutely infected MT-4 cells). Monoclonal antibodies were used for indirect immunofluorescence tests; the fluorescein-conjugated recombinant p14, the product of the HIV gene tat, was used as a molecular probe. The results demonstrated a high variability of FN and FNR expression among the various cellular lines studied. Moreover, deficits of such adhesive proteins did not necessarily correlate with a severe reduction of the corresponding receptor. HIV-1 replication in MT-4 and H9-V cells increased the expression of FNR. This seems to correlate with p14-induced phenomena because pretreatment of H9-V cells with recombinant p14 showed an enhancing effect on the expression of this receptor.

Amnion↗

Influence of fibronectin on HIV-1 infection and capability of binding to platelets.

We have previously demonstrated that fibronectin (FN) can bind HIV-1 envelope proteins, in particular gp 120. The aim of the present study was to determine some biological effects of this phenomenon. Pretreating HIV-1 with human FN increased the infectivity of HIV-1, when a low concentration of the virus was used. In contrast, an RGD-containing pentapeptide (Gly-Arg-Gly-Asp-Ser), which is a fundamental binding site of FN, reduced the infectivity of a suspension of HIV-1 at high concentrations of the virus. It is likely that FN bridges the cell surface and the virions, while the RGD-containing pentapeptide may saturate the HIV-1 binding sites for cell surface receptors. Moreover, gp 120 was bound to the FN present on the surface of platelets. The specificity of this binding was confirmed by the inhibition obtained by pretreating platelets with anti-FN antibodies. The consequence of the surface modifications of the platelets could explain the thrombocytopenia that frequently occurs in patients infected with HIV and suggests also the possibility that platelets could be a vehicle for the virus in the circulation.

Blood Platelets↗

The clinical use of 99m-Tc-labeled WBC scintigraphy in critically ill surgical and trauma patients with occult sepsis.

OBJECTIVE: To evaluate the clinical use of radionuclide-labeled white blood cell scintigraphy in the detection of focal sepsis. DESIGN: Prospective clinical study. SETTING: A medical/surgical 12-bed intensive care unit (ICU) in a university hospital. PATIENTS: 26 trauma and surgical patients affected by sepsis of unknown origin were studied. MEASUREMENTS AND RESULTS: After the usual diagnostic approach, patients were submitted to a total body scan by using the patient's leukocytes labeled with technetium-99m (99m-Tc) HMPAO; three scintigraphy were performed within 20 h of tracer injection; the result of scan was completed with all clinical and instrumental data, including ultrasound (US) arnd computed tomography (CT), and the diagnostic efficacy was demonstrated for each patient on discharge from the ICU. The scan was able to detect 20 sites of infection; it was possible to rule out 11 suspected sites; only in two cases was the result considered to be false positive or false negative; in two cases the result was considered to be uncertain. These results show the high sensitivity (95%), specificity (91%) and accuracy (94%) of the method. CONCLUSIONS: In ICU patients with sepsis, nuclear medicine can provide additional data, as the injection of radionuclide-labeled white blood cells (WBCs) allows the imaging of sites of infection. Analysis of our results suggests that scintigraphy with 99m-Tc-labeled WBCs can be considered a useful tool in the detection of the source of infection.

Adult↗

In vitro and in vivo induction of nitric oxide by murine macrophages stimulated with Bordetella pertussis.

Nitric oxide (NO) exhibits potent antimicrobial activity in vitro. The function of NO in host defenses in vivo, however, is presently unclear. Experiments were undertaken to determine the production of NO in vitro from murine peritoneal and alveolar macrophages, and murine macrophage cell line (J774A.1) stimulated with Bordetella pertussis or pertussis toxin (PT). In addition, we determined circulating levels of NO in the sera and bronchoalveolar lavage (BAL) fluids of mice infected intranasally with B. pertussis. The results of this study showed that in vitro murine peritoneal macrophages induce production of NO in response to B. pertussis and PT. In addition, murine macrophage cell line, J774A.1 also induces NO production after stimulation with B. pertussis. NO production was also detected in alveolar macrophages from mice infected intranasally with B. pertussis. Finally, a significant increment of circulating levels of NO was noted, in the sera but not in the BAL fluids, of mice infected intranasally with B. pertussis.

Administration, Intranasal↗

Immunological aspects of nitric oxide in HIV-1 infection.

Nitric oxide is produced in large amounts during host defense and immunological reactions and it is likely to have a role in non-specific immunity: nitric oxide exerts microbiostatic and microbicidal activity against a variety of pathogens, including protozoa, fungi, bacteria and some viruses. HIV-1 stimulates nitric oxide production by human macrophages and its production is increased in patients with HIV-1 infection. It is postulated that nitric oxide may play a part in modulating the immune response during HIV-1 infection. Nitric oxide produced by the HIV-1 infected monocytes/macrophages of lymph nodes, may adversely affect the survival of activated immune cells, including B and T lymphocytes and dendritic cells within their vicinity. It is suggested here that production of large amounts of nitric oxide by macrophages may lead to the inactivation of lymphocytes and thus to the induction of a persistent immunosuppression.

Acquired Immunodeficiency Syndrome↗

Increased levels of nitrite in the sera of children infected with human immunodeficiency virus type 1.

Nitric oxide (NO) is a newly discovered gas that plays an important role in cell communication and host resistance to infection. The production of NO was examined in the sera of seven children infected with human immunodeficiency virus type 1 (HIV-1) and in the sera of 14 children who became seronegative for HIV-1 during the first year of life. In addition, we determined serum levels of various cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, and gamma interferon (IFN-gamma), inasmuch as these cytokines are potent inducers of NO production. Production of NO, detected as circulating serum levels of nitrite, was measured with use of the Griess reagent. Serum levels of cytokines were determined by enzyme immunoassay. Increased serum levels of nitrite were observed in children with HIV-1 infection (0.4 +/- 0.2 mumol/L; P = .013), and in those who became seronegative for HIV-1 during the first year of life (0.5 +/- 0.3 mumol/L; P = .04). Furthermore, serum levels of IL-1 beta and TNF-alpha were significantly elevated in children with HIV-1 infection (37.5 +/- 23.6 pg/mL and 91.2 +/- 45.1 pg/mL, respectively). Prophylactic administration of intravenous immune globulin provoked a significant decrease of circulating levels of nitrite in children with HIV-1 infection. In conclusion, NO may play a role as a cytostatic or cytotoxic factor for invading microorganisms, and thus it is probably involved in limiting and/or eradicating infection.

Acquired Immunodeficiency Syndrome↗

Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis.

A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).

Adolescent↗

Effects of recombinant murine (rm) interleukin-12 and rm interferon-gamma in mice infected with Bordetella pertussis.

The recombinant cytokines interferon (IFN)-gamma and interleukin (IL)-12 stimulate several macrophage-mediated functions that are important in host defense. An experimental pertussis model showed that intraperitoneal (i.p.) administration of 10,000 U of recombinant murine (rm) IFN-gamma to mice at the time of Bordetella pertussis infection caused a marked and significant reduction in the number of colony-forming units of bacteria in the lungs. Administration i.p. of 1 microgram of rmIL-12 or 1 microgram of rmIL-12 at the time of and for 5 consecutive days after B. pertussis challenge also induced a significant reduction in the number. However, i.p. administration of 1 microgram of rmIL-12 with 10,000 U of IFN-gamma at the time of B. pertussis challenge did not provide protection. These findings indicate that exogenous administration of rmIL-12 and rmIFN-gamma enhances resistance of mice to B. pertussis infection.

Animals↗

Serum concentrations of nitrite in patients with HIV-1 infection.

AIMS: To measure circulating concentrations of nitrite in patients with HIV-1 infection. METHODS: Nitrite concentrations were measured using the Griess reaction adapted to microtitre plates in the serum of 10 asymptomatic HIV-1 positive patients, 33 patients with AIDS with cerebral disorders, 17 patients with AIDS with pulmonary involvement, and in eight patients with AIDS with other disorders. Nitrite concentrations were also measured in bronchoalveolar lavage (BAL) fluid and cerebrospinal fluid (CSF) of patients with AIDS with pulmonary involvement and cerebral disorders, respectively. RESULTS: Increased serum concentrations of nitrite were observed in patients with pulmonary involvement, and in particular in serum and in BAL samples of patients with interstitial pneumonia (36.2 (26.2) mumol/l and 0.3 (0.4) mumol/l, respectively). Increased serum concentrations of nitrite were also noted in patients with retinitis caused by infection with cytomegalovirus. Serum nitrite concentrations were also raised in patients with cerebral toxoplasmosis, whereas normal serum concentrations were found in patients with HIV-1 encephalopathy and cryptococcal meningitis. Nitrite concentrations in CSF were not raised in patients with cerebral disorders. CONCLUSIONS: These results suggest that production of nitrite in patients with AIDS with concomitant opportunistic infections may be part of the host defense against opportunistic organisms.

Adult↗

Expression of the alpha 5 beta 1 fibronectin receptor on T lymphocytes of patients with HIV-1 infection.

AIMS: To evaluate the expression of the alpha 5 beta 1 integrin fibronectin receptor (FNR), which mediates several processes, including phagocytosis, cell motility and the immune response, on T lymphocytes of patients with HIV-1 infection. METHODS: T lymphocytes were incubated with monoclonal antibody directed against FNR and then with monoclonal antibodies, conjugated with phycoerythrin, directed against CD3, CD4 and CD8 positive cells. Expression of FNR on CD3, CD4 and CD8 positive cells was analysed using flow cytometry. RESULTS: Normal expression of FNR was observed on CD3 positive cells from asymptomatic HIV positive patients and those with AIDS. Increased expression of FNR was observed on CD8 positive cells from asymptomatic HIV positive patients and on CD4 positive cells from patients with AIDS. Increased FNR expression was observed on CD4 positive cells from patients with AIDS, particularly those with opportunistic infections caused by Pneumocystis carinii, Mycobacterium sp, Toxoplasma gondii, and Cryptococcus neoformans. CONCLUSION: Increased expression of FNR on CD8 and CD4 positive cells in asymptomatic HIV positive patients and those with AIDS, respectively, may be an epiphenomenon correlated with lymphocyte activation by HIV-1 or opportunistic infection, Further study is required to determine whether upregulation of FNR expression has a direct role in the pathogenesis of AIDS.

AIDS-Related Opportunistic Infections↗